Issue 11, 2017
From the journal:

MedChemComm

Development of NMR and thermal shift assays for the evaluation of Mycobacterium tuberculosis isocitrate lyase inhibitors†

Ram Prasad Bhusal, ORCID logo a   Krunal Patel, ORCID logo a   Brooke X. C. Kwai, ORCID logo ‡a   Anne Swartjes, ORCID logo ‡ab   Ghader Bashiri, ORCID logo cd   Jóhannes Reynisson, ORCID logo a   Jonathan Sperry ORCID logo *a  and  Ivanhoe K. H. Leung ORCID logo *a  

* Corresponding authors

a School of Chemical Sciences, The University of Auckland, Private Bag 92019, Victoria Street West, Auckland 1142, New Zealand
E-mail: j.sperry@auckland.ac.nz (JS), i.leung@auckland.ac.nz (IKHL)

b Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, Nijmegen, The Netherlands

c School of Biological Sciences, The University of Auckland, Private Bag 92019, Victoria Street West, Auckland 1142, New Zealand

d Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Victoria Street West, Auckland 1142, New Zealand

Abstract

The enzymes isocitrate lyase (ICL) isoforms 1 and 2 are essential for Mycobacterium tuberculosis survival within macrophages during latent tuberculosis (TB). As such, ICLs are attractive therapeutic targets for the treatment of tuberculosis. However, there are few biophysical assays that are available for accurate kinetic and inhibition studies of ICL in vitro. Herein we report the development of a combined NMR spectroscopy and thermal shift assay to study ICL inhibitors for both screening and inhibition constant (IC50) measurement. Operating this new assay in tandem with virtual high-throughput screening has led to the discovery of several new ICL1 inhibitors.

Graphical abstract: Development of NMR and thermal shift assays for the evaluation of Mycobacterium tuberculosis isocitrate lyase inhibitors

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Article information

DOI
https://doi.org/10.1039/C7MD00456G
Article type
Research Article
Submitted
05 Sep 2017
Accepted
16 Oct 2017
First published
17 Oct 2017
This article is Open Access
Creative Commons BY-NC license

Med. Chem. Commun., 2017,8, 2155-2163

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Development of NMR and thermal shift assays for the evaluation of Mycobacterium tuberculosis isocitrate lyase inhibitors

R. P. Bhusal, K. Patel, B. X. C. Kwai, A. Swartjes, G. Bashiri, J. Reynisson, J. Sperry and I. K. H. Leung, Med. Chem. Commun., 2017, 8, 2155 DOI: 10.1039/C7MD00456G

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